Differential expression regulation of the α and β subunits of the PA28 proteasome activator in mature dendritic cells

Activation of dendritic cells (DC) by Th-dependent (CD40) or -independent (LPS, CpG, or immune complexes) agonistic stimuli strongly enhances the expression of the proteasome activator PA28 alpha beta complex. Upon activation of DC, increased MHC class I presentation occurred of the melanocyte-associated epitope tyrosinase-related protein 2(180-188) in a PA28 alpha beta-dependent manner. In contrast to other cell types, regulation of PA28 alpha beta expression in DC after maturation was found to be IFN-gamma independent. In the present study, we show that expression of PA28 alpha and beta subunits was differentially regulated. Firstly, PA28a expression is high in both immature and mature DC. In contrast, PA28 beta expression is low in immature DC and strongly increased in mature DC. Secondly, we show the presence of a functional NF-kappa B site in the PA28 beta promoter, which is absent in the PA28 alpha promoter, indicating regulation of PA28 beta expression by transcription factors of the NF-kappa B family. In addition, glycerol gradient analysis of DC lysates revealed elevated PA28 alpha beta complex formation upon maturation. Thus, induction of PA28 beta expression allows proper PA28 alpha beta complex formation, thereby enhancing proteasome activity in activated DC. Therefore, maturation of DC not only improves costimulation but also MHC class I processing. This mechanism enhances the CD8(+) CTL (cross)-priming capacity of mature DC.